The weight-loss drug market has been a hot topic in recent years, with blockbuster drugs like Eli Lilly's Zepbound and Novo Nordisk's Wegovy grabbing headlines. But more often than not, these drugs end up failing in development. Let's take a look at some of the most botched weight-loss drugs and learn from their failures.
Image source: Visual China
I. CASE STUDIES
(1) Pfizer Danuglipron: The "star candidate" on the safety issue
Danuglipron, Pfizer's highly anticipated oral GLP-1-based weight-loss drug, was originally the cornerstone of the company's weight management strategy. Initially, Pfizer pinned its hopes on Danuglipron due to liver toxicity risks observed in early-to-mid phase trials of another GLP-1 drug, Lotiglipron, while believing it could achieve "strong weight loss through complete receptor activation." However, the development path soon encountered setbacks: In December 2023, Pfizer had to discontinue the "twice-daily" dosing regimen—— during Phase IIb trials due to excessively high incidence of side effects. Notably, 73% of patients experienced nausea, with over 50% dropping out of the trial entirely. Although these adverse reactions were similar to those seen in other GLP-1 drugs, their staggering proportions raised significant concerns.
Pfizer persisted with its efforts, advancing the "once-daily" regimen in July 2024. However, by April 2024, the company discovered potential liver injury signals associated with danuglipron and halted its development entirely. Adding to the woes, Pfizer soon discontinued another weight-loss candidate drug, PF-06954522 (not due to safety concerns but based on assessments of Phase I trial data and GLP-1 market dynamics that deemed it uncompetitive), ending its portfolio of weight-loss medications. Despite these setbacks, Pfizer showed no signs of withdrawing from the GLP-1 race, announcing a new GLP-1 antibody-drug conjugate patent in May. Confronted with consecutive internal R&D failures, Pfizer explicitly stated it would seek external opportunities to strengthen its pipeline. During the Q2 earnings call, CEO Albert Bourla emphasized: "Obesity and cardiometabolic diseases remain key focus areas for the company."
(II) Roche CT-173:
In December 2023, Roche acquired Carmot for $2.7 billion to enter the weight-loss drug market. CT-173, one of the assets acquired in this deal, works by mimicking the body's PYY hormone to suppress appetite and regulate gastric motility. Early data showed promising results: A preclinical trial conducted in September 2024 demonstrated that combining CT-173 with Roche's another weight-loss candidate CT-388 enabled mice to overcome the "plateau phase" (a condition where weight loss becomes stagnant) and delayed post-discontinuation rebound. Roche also plans to initiate clinical trials for CT-173 in April 2025.
However, by July 2025, Roche stopped CT-173. The reason was that after evaluation, it did not meet the requirements of "r&d feasibility" and "market competitiveness", and could not compete with other drugs in the current weight-loss drug market. It was not cost-effective to continue investing money, so it cut losses in time.
(3) Amgen AMG 786: "The Underdog Candidate"
AMG 786 was Amgen's early-stage weight-loss drug candidate that never gained traction. Its Phase I trial, which ran from July 2022 to August 2023, enrolled 65 participants including healthy individuals and obese patients. In May 2024, Amgen abruptly halted AMG 786 development during an investor conference, citing "its lack of therapeutic value and unsupportable characteristics." The company shifted focus to another drug candidate, MariTide, but this also failed to meet market expectations—— Data from Phase II trials in November 2024 showed a maximum 20% weight loss over 52 weeks, falling short of investor expectations and causing Amgen's stock to plummet by 11%. The decline recovered only partially afterward. Additionally, Amgen's another candidate drug, AMG 513, faced trial suspension by the FDA. Although trials resumed in May 2025, this recovery brought new challenges to the development process.
（ four ）BioAgeazelaprag：
azelaprag, BioAge's flagship weight-loss candidate, works by activating the apelin receptor. Its early-stage data has been impressive: Phase 1 trials conducted in late 2022 demonstrated its ability to preserve muscle mass in bedridden patients (indicating it reduces fat rather than vital muscle tissue during weight loss, achieving "high-quality weight reduction"). In animal studies published in June 2024, when combined with Eli Lilly's Tepolizumab—a marketed weight-loss drug—the treatment doubled the weight loss efficacy in obese mice while restoring their body composition to levels comparable to lean mice.
The market is also bullish: BioAge raised $170 million in February 2024; started phase II trials (the STRIDES trial) in July 2024; and raised $238.3 million in an IPO in October 2024.
The reversal came swiftly: In December 2024, BioAge discovered that 11 patients using zelaprag developed "elevated liver transaminase levels" (a sign of liver damage or hepatitis), while the control group using only tiropride showed no such issues. This prompted an immediate termination of the Phase II trial. By January 2025, BioAge had completely abandoned zelaprag and shifted focus to alternative targets, including the NLRP3 signaling pathway associated with chronic inflammation linked to obesity.
(5) Boehringer Ingelheim BI 1820237:
In 2017, Boehringer Ingelheim invested approximately $292 million to acquire the development rights for BI 1820237 from Denmark's Gubra Pharmaceuticals. This neuropeptide Y receptor agonist was designed for weight management. Early trial results delivered positive signals: Phase I data released in May 2023 showed that in overweight males, both BI 1820237 alone and in combination with Novo Nordisk's liraglutide effectively reduced energy intake and slowed gastric emptying. These findings convinced Gubra to continue the research. Subsequent October 2024 data further confirmed that the combination with liraglutide significantly enhanced weight loss efficacy.
However, side effects became a major hurdle: In the October 2024 trial, 39% of participants reported adverse reactions, primarily gastrointestinal issues like nausea and vomiting. The biotech company discontinued development that same month, though three additional weight-loss projects in collaboration with Gubra (including a triple agonist with potential as a "first-in-class drug") continued progressing.
II. Reflection from failure cases
(1) Safety is the "red line" of weight-loss drug research and development
The case highlights three critical safety issues: Pfizer's danuglipron was discontinued due to potential liver damage, BioAge's azelaprag was withdrawn because of elevated liver enzymes, and BI 1820237 was terminated due to a 39% side effect rate. Even for mature targets like GLP-1 drugs, discontinuation becomes necessary when side effects become too severe (e.g., danuglipron's 73% nausea rate) or serious indicators like liver injury emerge—— Given the long-term nature of weight loss treatment, medications with unsecured safety cannot be sustainably used by patients, and such products would not gain market acceptance.
(2) The market competition is too fierce, and there is no "differentiation advantage"
In the current weight loss drug market, Eli Lilly and Novo Nordisk have secured first-mover advantages. Other drugs without unique features face easy elimination. Take Roche's CT-173 as an example: although it showed efficacy in combination with CT-388 in early mouse trials, human studies revealed it couldn't outperform existing drugs, leading to its abandonment. Pfizer's PF-06954522 was also discontinued not due to safety concerns but because it lacked competitiveness in the GLP-1 race. Even Terns' TERN-601 (showing 5% weight loss in Phase I over 28 days, comparable to Eli Lilly's orforglipron) was ultimately phased out as the company deemed it non-competitive in weight management, shifting focus to cancer drugs.
(3) Clinical data should be excellent, if the expectation can not keep up, there will be losses
The development of weight-loss drugs isn't about "relying on early positive data"; later clinical results must meet market expectations to maintain corporate confidence and stock value. Take Amgen's MariTide as an example: despite abandoning AMG 786 to fully invest in this drug, its Phase II trial showed a maximum 20% weight loss over 52 weeks—below investor expectations—which directly caused a 11% stock price drop. Similarly, BioAge's azelaprag, despite securing substantial funding and a successful IPO, saw its initial investments go down the drain when safety issues emerged during Phase II. These cases demonstrate that even the most promising early-stage drugs ultimately depend on later clinical data (particularly safety and efficacy) as their "hard currency" —any minor setback could derail the entire project.
(4) R&d strategies should be flexible, but it is difficult to adjust if the direction is wrong
Some companies adjust their R&D strategies based on pipeline priorities, such as Amgen shifting focus from AMG 786 to MariTide. However, misdirecting strategies can lead to disastrous consequences. Pfizer initially invested heavily in danuglipron but later faced safety concerns. Even after attempting to salvage the product by switching to a once-daily regimen, the company ultimately had to exit the weight-loss market entirely. Similarly, BioAge's pivot to a new target after abandoning azelaprag required significant time and financial investment – whether this path would succeed remains uncertain. Therefore, thorough pre-development target evaluation and market research are essential; otherwise, late-stage adjustments could become prohibitively costly.
Ref：
Official announcement of the company, Health Bureau, Medical Economic News, Sina Finance
www.BioSpace.com
www.fiercebiotech.com
Disclaimer: This article is only for the purpose of knowledge exchange and sharing, and does not involve commercial publicity, and does not serve as relevant medical guidance or medication advice. If there is any infringement, please contact us for deletion.
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